Residual solvent, reduction

The above syntheses of metal nanowires are based on the thermal hydrogen reduction. However, we found that the reproducible synthesis is difficult by this method, because the hydrogen reduction needs careful control of the reaction conditions. For the reproducible and selective synthesis of wires and particles, we need to clarify the factors controlling the sintering of metals. The key factors are the concentration of residual solvent and the relative rate of reduction and migration of metal ions. The details are shown in the next section. 

The most important multiply charged polyatomic positive ions are compounds with two or more basic groups which when protonated lead to doubly or poly-charged ions. Typical examples are diamines such as the double protonated a, to alkyldiamines, H3N(CH2)pNH2+, and the most important class, the polyprotonated peptides and proteins, which have multiple basic residues. Charge reduction for these systems occurs through proton transfer from one of the protonated basic sites to a solvent molecule. Such a reaction is shown below for the monohydrate of a doubly protonated diamine ... 

In some cases, a third stripper is operated in series of the two upstream stripper vessels, for further reduction of the residual solvent contents. 

When the supercritical fluid and drug solution make contact, a volume expansion occurs leading to a reduction in solvent capacity, increase in solute saturation, and then supersaturation with associated nucleation and particle formation. A number of advantages are claimed by using this platform technology (6), such as particle formation from nanometers to tens of micrometers, low residual solvent levels in products, preparation of polymorphic forms of drug, etc. 

The previous section discussed the mechanical hazards associated with operation of size-reduction equipment. There will also be hazards related to the feed material or product. These hazards can be associated with the solid product itself or with impurities, residual solvent, or the like. Several problems are covered below in separate sections ... 

The PGM concentrate is attacked with aqua regia to dissolve gold, platinum, and palladium. The more insoluble metals, iridium, rhodium, mthenium, and osmium remain as a residue. Gold is recovered from the aqua regia solution either by reduction to the metallic form with ferrous salts or by solvent-extraction methods. The solution is then treated with ammonium chloride to produce a precipitate of ammonium hexachloroplatinate(IV),... 

A flow diagram for the system is shown in Figure 5. Feed gas is dried, and ammonia and sulfur compounds are removed to prevent the irreversible buildup of insoluble salts in the system. Water and soHds formed by trace ammonia and sulfur compounds are removed in the solvent maintenance section (96). The pretreated carbon monoxide feed gas enters the absorber where it is selectively absorbed by a countercurrent flow of solvent to form a carbon monoxide complex with the active copper salt. The carbon monoxide-rich solution flows from the bottom of the absorber to a flash vessel where physically absorbed gas species such as hydrogen, nitrogen, and methane are removed. The solution is then sent to the stripper where the carbon monoxide is released from the complex by heating and pressure reduction to about 0.15 MPa (1.5 atm). The solvent is stripped of residual carbon monoxide, heat-exchanged with the stripper feed, and pumped to the top of the absorber to complete the cycle. 

Estrone methyl ether (100 g, 0.35 mole) is mixed with 100 ml of absolute ethanol, 100 ml of benzene and 200 ml of triethyl orthoformate. Concentrated sulfuric acid (1.55 ml) is added and the mixture is stirred at room temperature for 2 hr. The mixture is then made alkaline by the addition of excess tetra-methylguanidine (ca. 4 ml) and the organic solvents are removed. The residue is dissolved in heptane and the solution is filtered through Celite to prevent emulsions in the following extraction. The solution is then washed threetimes with 500 ml of 10 % sodium hydroxide solution in methanol to remove excess triethyl orthoformate, which would interfere with the Birch reduction solvent system. The heptane solution is dried over sodium sulfate and the solvent is removed. The residue is satisfactory for the Birch reduction step. Infrared analysis shows that the material contains 1.3-1.5% of estrone methyl ether. The pure ketal may be obtained by crystallization from anhydrous ethanol, mp 99-100°. Acidification of the methanolic sodium hydroxide washes affords 10-12 g of recovered estrone methyl ether. 

The crude ketal from the Birch reduction is dissolved in a mixture of 700 ml ethyl acetate, 1260 ml absolute ethanol and 31.5 ml water. To this solution is added 198 ml of 0.01 Mp-toluenesulfonic acid in absolute ethanol. (Methanol cannot be substituted for the ethanol nor can denatured ethanol containing methanol be used. In the presence of methanol, the diethyl ketal forms the mixed methyl ethyl ketal at C-17 and this mixed ketal hydrolyzes at a much slower rate than does the diethyl ketal.) The mixture is stirred at room temperature under nitrogen for 10 min and 56 ml of 10% potassium bicarbonate solution is added to neutralize the toluenesulfonic acid. The organic solvents are removed in a rotary vacuum evaporator and water is added as the organic solvents distill. When all of the organic solvents have been distilled, the granular precipitate of 1,4-dihydroestrone 3- methyl ether is collected on a filter and washed well with cold water. The solid is sucked dry and is dissolved in 800 ml of methyl ethyl ketone. To this solution is added 1600 ml of 1 1 methanol-water mixture and the resulting mixture is cooled in an ice bath for 1 hr. The solid is collected, rinsed with cold methanol-water (1 1), air-dried, and finally dried in a vacuum oven at 60° yield, 71.5 g (81 % based on estrone methyl ether actually carried into the Birch reduction as the ketal) mp 139-141°, reported mp 141-141.5°. The material has an enol ether assay of 99%, a residual aromatics content of 0.6% and a 19-norandrost-5(10)-ene-3,17-dione content of 0.5% (from hydrolysis of the 3-enol ether). It contains less than 0.1 % of 17-ol and only a trace of ketal formed by addition of ethanol to the 3-enol ether. 

The reduction is effected exactly as in Procedure 8a but using 0.61 g (0.088 g-atom) of lithium. After the crude reaction product has been washed well on the filter with cold water, it is dissolved in ethyl acetate, the solution is filtered through the sintered glass funnel to remove iron compounds from the ammonia, and the filtrate is extracted with saturated salt solution. The organic layer is dried over sodium sulfate and the solvent is removed. The solid residue is crystallized from methanol (120 ml) using Darco. The mixture is cooled in an ice-bath, the solid is collected, rinsed with cold methanol, and then air-dried to give 12.9 g (85%), mp 129-132° reported for the tetrahydropyranyi ether of 3j5-hydroxypregn-5-en-20-one, mp 129-131°. 

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